Faculty Bibliography

Objective: This is one of two separate clinical trials to evaluate the efficacy and safety of modafinil, a novel wake-promoting agent, inpatients with excessive daytime sleepiness (EDS) associated with narcolepsy. Methods: In this 9-week, randomized, placebo-controlled, double-blind, 21-center clinical trial, patients were randomized to receive fixed daily doses of modafinil 200 mg, modafinil 400 mg, or placebo. A placebo-controlled, 8-week treatment discontinuation phase was included to evaluate the effects of withdrawal on patients who had been receiving modafinil. A total of 271 patients who were naive to modafinil received study medication:in the 9-week trial and 240 patients received;study medication in the discontinuation phase. Results: Treatment with modafinil resulted in significant improvement in two objective measures of E

Varying approaches to measuring the respiratory disturbance index (RDI) may lead to discrepant estimates of the severity of sleep-disordered breathing (SDB). In this study, we assessed the impact of varying the use of corroborative data (presence and degree of desaturation and/or arousal) to identify hypopneas and apneas. The relationships among 10 RDIs defined by various definitions of apneas and hypopneas were assessed in 5,046 participants in the Sleep Heart Health Study (SHHS) who underwent overnight unattended 12-channel polysomnography (PSG). The magnitude of the median RDI varied 10-fold (i.e., 29.3 when the RDI was based on events identified on the basis of flow or volume amplitude criteria alone to 2.0 for an RDI that required an associated 5% desaturation with events). The correlation between RDIs based on different definitions ranged from 0.99 to 0.68. The highest correlations were among RDIs that required apneas and hypopneas to be associated with some level of desaturation. Lower correlations were observed between RDIs that required desaturation as compared with RDIs defined on the basis of amplitude criteria alone or associated arousal. These data suggest that different approaches for measuring the RDI may contribute to substantial variability in identification and classification of the disorder

The contribution of apnea to chronic hypercapnia in obstructive sleep apnea (OSA) has not been clarified. Using a model (D. M. Rapoport, R. G. Norman, and R. M. Goldring. J. Appl. Physiol. 75: 2302-2309, 1993), we previously illustrated failure of CO(2) homeostasis during periodic breathing resulting from temporal dissociation between ventilation and perfusion ('temporal V/Q mismatch'). This study measures acute kinetics of CO(2) during periodic breathing and addresses interapnea ventilatory compensation for maintenance of CO(2) homeostasis in 11 patients with OSA during daytime sleep (37-171 min). Ventilation and expiratory CO(2) and O(2) fractions were measured on a breath-by-breath basis by means of a tight-fitting full facemask. Calculations included CO(2) excretion, metabolic CO(2) production, and CO(2) balance (metabolic CO(2) production - exhaled CO(2)). CO(2) balance was tabulated for each apnea/hypopnea event-interevent cycle and as a cumulative value during sleep. Cumulative CO(2) balance varied (-3,570 to +1,388 ml). Positive cumulative CO(2) balance occurred in the absence of overall hypoventilation during sleep. For each cycle, positive CO(2) balance occurred despite increased interevent ventilation to rates as high as 45 l/min. This failure of CO(2) homeostasis was dependent on the event-to-interevent duration ratio. The results demonstrate that 1) periodic breathing provides a mechanism for acute hypercapnia in OSA, 2) acute hypercapnia during periodic breathing may occur without a decrease in average minute ventilation, supporting the presence of temporal V/Q mismatch, as predicted from our model, and 3) compensation for CO(2) accumulation during apnea/hypopnea may be limited by the duration of the interevent interval. The relationship of this acute hypercapnia to sustained chronic hypercapnia in OSA remains to be further explored

STUDY OBJECTIVES: We addressed the issue of how commuting affects sleep habits, and its association with general health and potential sleep disorders in individuals on a large, U.S. commuter rail system. DESIGN: Postage-paid mail back questionnaires were distributed to commuters over 6 consecutive weekdays. The questionnaire incorporated previously validated questions regarding sleep habits. SETTING: Questionnaires were dispensed at 15 different rail stations. PARTICIPANTS: 21,000 commuters accepted the questionnaire. MEASUREMENTS AND RESULTS: Data was analyzed by total group and length of commute. A total of 4715 (22%) questionnaires were returned. Over 50% of the sample reported difficulty with sleep and wakefulness while only 3% sought professional help. Sleep apnea was suspected in 4.2% of male and 1% of female respondents and was associated with increased reports of excessive daytime sleepiness, and history of hypertension, diabetes and obesity. Total nocturnal sleep time was significantly less in those subjects with long commutes. Seventy percent of respondents reported napping during the commute. Length of commute was associated with hypertension. CONCLUSION: Commuting long distances negatively impacts one's ability to capture adequate sleep. Data suggests that there may be significant numbers of respondents with unrecognized sleep disorders which further impact on general health

Therapeutic decisions in patients with sleep apnea (eg, adjustment of continuous positive airway pressure [CPAP]) depend on differentiating central from obstructive apnea. Obstructive apnea is defined by cessation of airflow in the presence of continued respiratory effort, which is conventionally inferred from chest wall movement or intrathoracic pressure swings. Cardiogenic oscillations in the airflow have been observed during some central apneas, but there is controversy over whether they correlate with airway patency. The present study investigates whether these oscillations are markers of the absence of respiratory effort (central apnea) without regard to airway patency. METHODS: We examined 648 apneas in 52 patients undergoing nocturnal polysomnograms and CPAP titrations. Airflow was measured using the output of the CPAP generator, and apneas were identified from reduction of airflow to < 10% for > 10 s. We used only the presence or complete absence of thoracoabdominal motion to classify apneas: obstructive apnea when motion was present (297 apneas); and central apnea if motion was totally absent (351 apneas). Central apneas most often occurred at sleep onset or followed arousal with a big breath. Using only the flow signal, all apneas were examined for the presence of cardiogenic oscillation by an observer blinded to other signals and apnea types. RESULTS: No obstructive apnea showed definite cardiogenic oscillations. In four cases, there was a suggestion of oscillation that was not regular enough to be called cardiac. Sixty percent of central apneas showed clear, regular oscillations at cardiac frequency. Cardiogenic oscillations also were seen intermittently during quiet exhalation in apnea-free periods. CONCLUSION: The presence of cardiogenic oscillations on the CPAP flow signal is a specific indicator of central apnea and may have a role in self-titrating CPAP algorithms. We speculate that transmission of these cardiac-induced oscillations may relate to the relaxation of thoracic muscles during central apnea and is impeded by high muscle tone during obstructive apnea

This paper reviews the data collection, processing, and analysis approaches developed to obtain comprehensive unattended polysomnographic data for the Sleep Heart Health Study, a multicenter study of the cardiovascular consequences of sleep-disordered breathing. Protocols were developed and implemented to standardize in-home data collection procedures and to perform centralized sleep scoring. Of 7027 studies performed on 6697 participants, 5534 studies were determined to be technically acceptable (failure rate 5.3%). Quality grades varied over time, reflecting the influences of variable technician experience, and equipment aging and modifications. Eighty-seven percent of studies were judged to be of 'good' quality or better, and 75% were judged to be of sufficient quality to provide reliable sleep staging and arousal data. Poor submental EMG (electromyogram) accounted for the largest proportion of poor signal grades (9% of studies had <2 hours artifact free EMG signal). These data suggest that with rigorous training and clear protocols for data collection and processing, good-quality multichannel polysomnography data can be obtained for a majority of unattended studies performed in a research setting. Data most susceptible to poor signal quality are sleep staging and arousal data that require clear EEG (electroencephalograph) and EMG signals